tbuckley/cabot-search huggingface dataset:
Dedicated overseas consultation for patients evacuated from the south Pacific: Report of experience after six months of existence.
Authors: Nicolas Epaillard, Arthur Geraud, Gabriel Garcia, Ronan Flippot, Laury Cherot, Benjamin Besse, Felix Blanc-Durand, Kaissa Ouali, Linda Mahjoubi, Emilie Routier, Gianmaria Drovetti, Pierre Gustin, Margarida Matias, Jean François Moulin, Simon Azan, Robert Herve, Barbara Pistilli, Emeline Colomba, Michel Pierre Ducreux, Charles Honoré
Journal: Journal of Clinical Oncology (2023)

e18542 Background: The management of rare and/or complex cancers between patients living in metropolitan France and those living overseas remains unequal. Herein, medical transfer to metropolitan France is required in about 20% of overseas-living patients and is often experienced as an additional source of distress, which requires multidisciplinary support (social, psychological, medical, and cultural). Therefore, we developed a dedicated “Overseas” consultation (OC) to provide personalized cancer care in this specific population. We aim to present the evaluation of the first 6 months experience. Methods: The OC was dedicated to patients from the South Pacific (French Polynesia or New Caledonia) requiring “highly specialized” cancer treatments in Gustave Roussy, including surgery, chemotherapy, or diagnostic procedures, which were considered non-achievable in the local hospital after multidisciplinary discussion by videoconference. Multiple interventions including medical, administrative and psychological support were provided. Results: Between July 15, 2022, and January 15, 2023, 25 patients with rare and/or complex cancer diagnosis / treatments benefited from an OC. Median age was 57 years (30-81), 19 patients (76%) were women, 18 (72%) came from French Polynesia and 7 (28%) from New Caledonia. Median number of OC for each patient was 1 (range 1-3), and median length of stay in metropolitan France was 23 days (range 4-95 days). At the time of analysis, 7 patients had not yet returned back home. The most common cancer locations were breast (52%), lung (16%) and gastrointestinal (16%). Patient presented localized disease in 52% of cases. At the first OC, 92% patients were ECOG Performance Status 0-1. The main reasons for metropolitan France medical transfer were an imaging procedure (64%) or a complex surgical or interventional radiology biopsy (24%). Seven patients (28%) had complex management (defined as two or more procedures) during their stay. Eleven patients (44%) benefited from molecular profiling, 7 (27%) from an oncogenetic consultation and 1 (4%) from inclusion in a clinical research trial. Conclusions: OC, set up 6 months ago in our institution, has optimized diagnostic workflow and disease management of these complex patients living overseas and has demonstrated its feasibility. However, it requires the involvement of multiple health-care professionals, multidisciplinary concertation, paramedical interventions such as social and psychological support and the overarching support from institutions.
Circulating tumor DNA as a marker of recurrence risk in locoregional esophagogastric cancers with pathologic complete response.
Authors: Eric Michael Lander, Brandon Huffman, Samuel J Klempner, Vasily N. Aushev, Jenifer Ferguson, Shruti Sharma, Adham A Jurdi, Minetta C. Liu, Cathy Eng, Michael K. Gibson
Journal: Journal of Clinical Oncology (2023)

4066 Background: Following neoadjuvant therapy and definitive surgery, up to one-third of patients (pts) with gastroesophageal adenocarcinoma with a pathologic complete response (pCR; tumor regression grade 0 [TRG0]) will recur, while up to one-half of pts with a near-pCR (TRG1) experience recurrence. Our study aims to evaluate postoperative circulating tumor DNA (ctDNA) as a prognosticator of recurrence in pts with pCR or near-pCR after curative-intent neoadjuvant chemotherapy (NAC) or chemoradiation (CRT) and surgery. Methods: We retrospectively identified pts from 11 institutions with stages I-III esophagogastric cancers who completed neoadjuvant therapy and had TRG0 or TRG1 scores at the time of curative-intent surgery. Postoperative plasma samples were collected for ctDNA analysis within a 16-week molecular residual disease (MRD) window after definitive surgery and serially during follow-up from 9/19/19 to 2/21/22. MRD by ctDNA was assessed using a personalized, tumor-informed ctDNA assay (Signatera mPCR-NGS assay). The primary outcome was recurrence-free survival (RFS), measured from the date of surgery to the first documented sign of radiographic recurrence. Survival analysis was performed using the maximum likelihood bias reduction method for Cox regression. Results: We obtained 250 blood samples from 45 pts with esophageal (N=18), gastroesophageal junction (N=17), and gastric (N=10) adenocarcinomas who received either NAC or CRT. The median follow-up for this cohort was 22.8 months (range: 0.3-81.7 months). Despite pts achieving pCR (N=12) or near-pCR (N=33), ctDNA-positivity in the 16-week MRD window (N=21) correlated with higher rates of recurrence (66.7%; 2/3) compared to the absence of ctDNA (11.1%; 2/18). Detectable ctDNA was associated with a significantly shorter RFS (HR 23.0, 95% CI 2.0-268.1; p=0.012). 35 pts had ctDNA analyzed at any post-surgical time point, where the recurrence rate was 87.5% (7/8) in ctDNA-positive pts compared to 7.4% (2/27) in ctDNA-negative pts, exhibiting a further reduction in RFS (HR 44.8; 95% CI 5.4-369.7; p&lt;0.0001). Out of 8 ctDNA-positive pts, two (25%) converted from ctDNA-positive to ctDNA-negative with subsequent treatment. Conclusions: Within the subgroup of pts with esophagogastric adenocarcinoma and favorable pathologic responses (TRG 0-1) following neoadjuvant treatment, the presence of post-operative ctDNA identified pts with elevated recurrence risk. If validated in larger cohort studies, testing for ctDNA may be a useful biomarker to select pts at risk for recurrence with potential to inform prospective clinical trials for direction of adjuvant therapy.
Combined associations of a healthy lifestyle and body mass index on colorectal cancer recurrence and survival: A cohort study.
Authors: Shabane Barot, Petri Rantanen, Caroline Nordenvall, Ulrik Lindforss, Asa Hallqvist Everhov, Susanna Larsson, Annika Lindblom, Annelie Liljegren
Journal: Journal of Clinical Oncology (2023)

3609 Background: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a pre-diagnostic healthy lifestyle and body mass index (BMI) on prognosis following CRC diagnosis. Methods: Treatment and follow-up data were collected from the patient files of 1098 participants from the Swedish Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI five years before diagnosis, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards model, the latter adjusted for age, sex, and educational level. Results: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score of 4 (most healthy). Participants missing follow-up data (n = 29) or relapsing ≤ 6 months (n = 29) were excluded from the recurrence-free survival analysis. 221 events of cancer recurrence were observed among 1040 participants during a median follow-up time of 4.3 years, and 542 deaths among 1098 participants during a median follow-up time of 6.3 years. Patients with the healthiest lifestyle had an improved recurrence-free survival (HL 4 vs HL0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70)). Stratifying these results for cancer stage (I-III) and tumor site (colon/rectum) did not alter estimated HR:s or 95% CI:s. Avoidance of smoking and being physically active were independently associated with improved recurrence-free survival and overall survival: non-smoking vs smoking HRadj 0.62 (95% CI 0.43-0.90), high vs low levels of physical activity HRadj 0.71 (95% CI 0.54-0-94)). Conclusions: Our study indicates that pre-diagnostic adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC. Avoidance of smoking and being physically active were the strongest risk-reducing factors for these outcomes. [Table: see text]
Capturing age-related changes in the tumor microenvironment of luminal breast cancer using the multiplex immunohistochemistry technique, MILAN.
Authors: Yentl Lambrechts, Asier Antoranz Martinez, Maxim De Schepper, Tatjana Geukens, Hanne Vos, Lieze Berben, Julie Messiaen, Lukas Marcelis, Yannick Van Herck, Patrick Neven, Ann Smeets, Kevin Punie, Christine Desmedt, Francesca Maria Bosisio, Frederik De Smet, Sigrid Hatse, Hans Wildiers, Giuseppe Floris
Journal: Journal of Clinical Oncology (2023)

e15089 Background: The ‘immune landscape’ of luminal breast tumors is poorly described to date. We applied the ‘multiple iterative labeling by antibody ‘neodeposition’ (MILAN) technique for in-depth characterization of the tumor microenvironment of luminal-like breast cancer (BC) in relation to age. Methods: Newly diagnosed patients with early luminal BC (grade 2/3, ER+, HER2-, tumor size ≥1,5 cm) were prospectively included in UH Leuven between March 2014 and November 2015 and divided into 3 distinct age categories (young: 35-45 yrs.; middle: 55-65 yrs.; old: ≥70 yrs.). 55 patients (young: n = 12; middle: n = 16; old: n = 27) were included in the cohort. From each patient up to 2 cores from the tumor center (TC) and 2 cores from the invasive front (IF) were sampled from formalin-fixed and paraffin-embedded tumor resection specimens and embedded in tissue microarrays. The MILAN workflow included 20 rounds of three-color indirect immunofluorescence (FITC, TRITC, and Cy5 channel combined with 58 antibodies), image acquisition, and removal/stripping of the antibodies before any other stain. The MILAN data analysis pipeline was applied to study the expression of phenotypic and functional proteins at single-cell level including spatial resolution. These were compared between the different age groups using Wilcoxon's test (FDR correction). Results: We identified 1,5 million cells, of which 59% were epithelial cells (cancer and normal), 29% were immune cells, and the remaining 12% were endothelial or stromal cells. Within the immune cell fraction, T-helper (Th) cells, B-cells, T-cytotoxic (Tcy) cells, and NK-cells significantly decreased with aging while monocytes significantly increased in TC and IF (Table 1). The evaluation of the functional markers in the inflammatory cells revealed a decreased expression with aging of PD-L1 in Tcy cells (p &lt; 0.001 for TC and IF), Th cells (p = 0.003 for IF), T-regulatory (Treg) cells (p = 0.038 for TC), monocytes (p &lt; 0.001 for TC and IF), and B-cells (p = 0.023 for TC). Perforin expression significantly decreased with aging in Th cells (p &lt; 0.05 for TC and IF) and monocytes (p &lt; 0.001 for TC and IF). OX-40 expression significantly decreased with aging in Th cells (p = 0.001 for TC), Treg cells (p = 0.002 for TC), and B-cells (p = 0.012 for TC). Conclusions: Our results suggest important compositional and functional changes in the tumor inflammatory microenvironment during aging in patients with luminal BC. Further analysis on other cell types is warranted. [Table: see text]
Association of nutrition with psychological health and quality of life among older adults with advanced cancer.
Authors: Surbhi Singhal, Zhaoyang Qin, Derick R. Peterson, Richard Francis Dunne, Ying Wang, Eva Culakova, Valerie Targia, Nataliya Melnyk, Adedayo A. Onitilo, Alison Katherine Conlin, Supriya Gupta Mohile, Kah Poh Loh
Journal: Journal of Clinical Oncology (2023)

12043 Background: Impaired nutrition is associated with greater treatment toxicity and reduced overall survival in patients with advanced cancer. We aimed to evaluate the association of impaired nutrition with psychological health and quality of life among older adults with advanced cancer who were starting cancer treatment with palliative intent. Methods: This secondary analysis was performed on baseline data from a nationwide cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02107443; PI: Mohile; funding NCI UG1CA189961). Adults age ≥70 with advanced cancer and≥1 geriatric assessment impairment were enrolled from 2014 to 2017. Patients with BMI &lt; 21 kg/m 2 , &gt; 10% involuntary weight loss in the past 6 months, or Mini Nutritional Assessment Short Form (MNA-SF) score of ≤11 were considered to have impaired nutrition. We used separate multivariable linear regressions to evaluate the association of impaired nutrition with each measure of psychological health and quality of life, which included Geriatric Depression Scale (GDS-15, range 0-15), Generalized Anxiety Disorder-7 (GAD-7, range 0-21), NCCN Distress Thermometer (NCCN DT, range 0-10) and Functional Assessment of Cancer Therapy-General (FACT-G, range 0-108). Analyses were adjusted for baseline patient demographics, clinical characteristics, and geriatric assessment. Results: Among 541 patients, mean age was 77 (range 70-96) and 60% had impaired nutrition. Among the 326 patients with impaired nutrition, 95% had MNA-SF ≤11, 23% had &gt; 10% weight loss in the last six months, and 20% had BMI &lt; 21 kg/m 2 . Mean baseline GDS-15 was 3.1 (standard deviation [SD] 2.7), GAD-7 was 2.9 (SD 4.0), NCCN DT was 2.9 (SD 2.7), and FACT-G was 80 (SD 14). In the adjusted model, compared to those with normal nutrition, older adults with impaired nutrition had greater depression (mean 0.65 points higher on the GDS-15, p &lt; 0.01) and lower quality of life (mean 6.0 points lower on the FACT-G, p &lt; 0.01). There was insufficient evidence of an association between nutrition and anxiety (β = 0.67, p = 0.06) or distress (β = 0.26, p = 0.28). Conclusions: Recognition of malnutrition by oncology providers is crucial for older adults with advanced cancer. Impaired nutrition is associated with greater depression and lower quality of life among older adults with advanced cancer. Tailored resources to improve psychological health and quality of life are needed to support older adults with impaired nutrition receiving cancer treatment.
Regorafenib second-line therapy for surgical recurrent hepatocellular carcinoma: An exploration of continuing regorafenib therapy after tumor progression—A single-center retrospective analysis of 90 cases.
Authors: Liqun Wu, Wei Rao, Ge Guan, Yang Xin, Qinghui Niu, Ning Fan, Yuan Guo, Zixiang Li, Song Wang, Jinzhen Cai
Journal: Journal of Clinical Oncology (2023)

e16164 Background: To explore the prognosis of patients with continuing regorafenib therapy after the HCC progression of second-line regorafenib therapy. Methods: The HCC patients with second treatment by regorafenib from Dec. 2017 to Dec. 2021 were collected from His system of the hospital. The inclusion criteria included surgical treatment with hepatectomy or liver transplantation, the HCC diagnosis by pathological confirmed, Child-Pugh A-B and ECOG PS≤2 when taking regorafenib, exposure time ≥21 days. Efficacy was evaluated according to RECIST v1.1 (solid tumor efficacy Evaluation Criteria). Results: By Dec. 31, 2022, the median follow-up time was 17.6 months since taking regorafenib. The median overall survival (OS) time was 26.0 months (95%CI 19.75-32.25 months) in 110 patients with second-line regorafenib treatment for recurrent HCC after surgical treatment, and the median OS time of first-line sequential regorafenib was 37.6 months (95%CI 30.23-44.97 months). In 100 cases of regorafenib progression, 10 cases received only palliative therapy after progression. The ninety cases continued the antitumor therapy, the median OS time after progression was 18.0 months (95%CI 12.93-23.07). There were 56 patients (62.2%) who continued to take regorafenib and 34 patients (37.8%) who took other targeted drugs. The median OS time after progression in the two groups was 18.0 and 19.8 months, respectively (P=0.614). In 56 patients who continued regorafenib, Kaplan-Meier analysis and Cox regression risk model analysis showed that NLR≥4.0, liver tumor load larger and without combination therapy were independent risk factors for survival after progression in patients with continued regorafenib. Conclusions: The overall survival time 18.0 months was found in patients with HCC progression after second-line regorafenib therapy, these patients with recurrent HCC underwent surgical treatment (resection or liver transplantation). There was no significant difference in OS time between those who continued regorafenib therapy and those who selected other targeted agents after HCC progression with the regorafenib. The NLR≥4.0, liver tumor load lager, and without combination therapy were independent risk factors for survival after progression in patients who continued regorafenib.
LungFlag, a machine-learning (ML) personalized tool for assessing lung cancer risk in a community setting, to evaluate performance in flagging non-small cell lung cancer (NSCLC) regardless of sex or race.
Authors: David Morgenstern, Eran Netanel Choman
Journal: Journal of Clinical Oncology (2023)

10570 Background: Application of ML-based risk prediction models to lung cancer screening cohorts have been shown to increase screening efficiency. However, ML-based models may be vulnerable to sexual and racial bias arising from historical bias in health care access as well as biased training data. Demonstrating fairness in the predictions of ML-based models is a prerequisite to their acceptance by clinicians and patients. We assessed the clinical performance of LungFlag based on sex and race, two key demographic subgroups at risk for disparate outcomes due to bias. Methods: The LungFlag machine learning model is a retrospectively validated ML model intended to identify individuals who are at elevated risk for lung cancer and should be counseled regarding lung cancer screening. LungFlag uses existing routine outpatient lab measurements, smoking history, comorbidities, and demographic data to flag high-risk individuals. We compare performance of LungFlag between sexes and between races and calculate the sensitivity at the overall positivity rate of 3%. We chose a case-control design based on a large US-based community and outpatient dataset including 39,135 case patients with NSCLC and 212,454 contemporaneous NSCLC-free controls. We included ever-smokers, ages 45-80, with available lab measurements from 3-12 months before diagnosis, and minimal follow-up of 24 months. Sub-populations with less than 1% representation from the total population were excluded. Results: The comparison between the sub-populations presented by sensitivity and specificity indexes is detailed in the table. No statistically significant difference was demonstrated in the sensitivity of the model to flag individuals that were diagnosed with NSCLC on multiple sub-populations. Conclusions: The LungFlag model demonstrated fairness with respect to sex and race based on similar clinical sensitivity in a large, community-based retrospective dataset. Further assessment in prospective studies and in additional racial sub-populations is recommended to support this conclusion. [Table: see text]
Final overall survival analysis of JUPITER-02: A phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).
Authors: Hai-Qiang Mai, Qiu-Yan Chen, Dong-Ping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jin-Gao Li, Yingrui Shi, Feng Jin, Ruilian Xu, Jian-ji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Darren Wan-Teck Lim, Rui-Hua Xu
Journal: Journal of Clinical Oncology (2023)

6009 Background: There are currently no FDA-approved IO therapies for NPC. Toripalimab in combination with Gemcitabine-Cisplatin (GP) chemotherapy had shown significant improvement over chemotherapy alone in progression-free survival (PFS) as first-line treatment for recurrent or metastatic (r/m) NPC at the interim PFS analysis of JUPITER-02 (NCT03581786) study. The final overall survival (OS) analysis results are summarized here. Methods: Patients with r/m NPC (n = 289) were randomized (1:1) to receive toripalimab 240 mg (n = 146) or placebo (n = 143) in combination with GP once every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG performance score (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. The primary endpoint was PFS by an independent review committee. Secondary endpoints included OS and safety. Results: By the cutoff date of Nov 18, 2022, when 133 events were reached for the final OS analysis, the median survival follow up was 30.1 months. A significant improvement in OS was observed for the toripalimab arm over the placebo arm: HR = 0.63 (95% CI: 0.45-0.89), two-sided p = 0.0083. The median OS was not reached in the toripalimab arm and was 33.7 months in the placebo arm. The 2-year and 3-year OS rates were 78.0% vs. 65.1%, and 64.5% vs. 49.2% respectively. A consistent effect on OS, favoring the toripalimab arm, was observed in nearly all subgroups, including PD-L1 high and PD-L1 low expression subgroups. No new safety signals were identified in the toripalimab arm since the interim report. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (3.4% vs 2.8%) were similar between two arms. However, AEs leading to discontinuation of toripalimab/placebo (11.6% vs 4.9%), immune-related (irAEs) (54.1% vs. 21.7%) and Grade ≥3 irAEs (9.6% vs. 1.4%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1 st -line treatment for r/m NPC provided clinically important and highly significant OS advantage over GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786 .